1. Field of the Invention
All of the nonsteroidal anti-inflammatory drugs in current use inhibit both 5-lipoxygenase activity and 15-lipoxygenase activity. These enzymes are involved in prostaglandin biosynthesis and in lipoxin biosynthesis, respectively. Thus, these drugs effect a broad range of activities. In addition, most have side-effects related to irritation of the stomach. This invention relates to compounds which inhibit only the lipoxin biosynthetic pathway. This degree of specificity is very useful in treating atherosclerosis and asthma since the etiology of both pathological conditions involve a 15-lipoxygenase.
2. Description of the Related Art
Hopanoids are lipids which are pentacyclic triterpene derivatives of hopane. The compounds are cyclic and branched and are therefore generally considered very stable. They have been found preserved in the organic matter of sedimentary material with only small structural changes. They have thus been successfully utilized as biomarkers in geological sediments (Ourisson et al. 1984. Annu. Rev. Microbiol. vol 47, pp. 301-333; Ourisson et al. 1979. Pure Appl. Chem. vol. 51, pp. 709-729).
Hopanoids are also found in numerous species of bacteria and cyanobacteria (Rohmer et al. 1984. J. Gen. Microbiol. vol. 130, pp. 1137-1150), some species of fungi (Tsuda and Isobe. 1965. Tetrahedron Lett. vol. 27, pp. 709-729; van Eijk et al. 1986. Tetrahedron Lett. vol. 27, pp. 2522-2534), lichens (Ejiri and Shibata. 1974. Phytochemistry. vol. 13, p. 2871) and a few species of higher plants (Ourisson et al. 1979, supra). They are localized in bacterial membranes and, since they possess some structural similarity to sterols which are known membrane stabilizers in eukaryotes (Ourisson et al. 1984, supra), they have been implicated in both prokaryotic and eukaryotic membrane stabilization.
In addition, some hopanoids have been reported to show anti-tumor cell effects. Nagumo et al. (1991. Toxicol. Lett. vol. 58, pp. 309-313) tested the cytotoxicity of a hopanoid isolated from Rhodopseudomonas palustris against mouse leukemia cells, and Chen et al. (1995. Biol. Pharm. Bull., vol. 18, no. 3, pp. 421-423) investigated cytotoxic effects of a number of hopanoids isolated from Acetobacter aceti, also against mouse leukemia cells.
Heretofore, there have been no reports or suggestions of anti-inflammatory activity exhibited by hopanoid compounds.